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Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
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2015 (English)In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 23, no 4, 295-306 p.Article in journal (Refereed) Published
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Abstract [en]

Aims: Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function. Results: Long-term dietary supplementation with sodium nitrate (0.1 and 1mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose. Innovation and Conclusions: These results demonstrate the existence of a cross-talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis. Antioxid. Redox Signal. 23, 295-306.

Place, publisher, year, edition, pages
2015. Vol. 23, no 4, 295-306 p.
National Category
Endocrinology and Diabetes Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
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URN: urn:nbn:se:uu:diva-268717DOI: 10.1089/ars.2013.5481ISI: 000363895200002PubMedID: 24224525OAI: oai:DiVA.org:uu-268717DiVA: diva2:878797
Funder
Swedish Research Council, K2012-99X-21971-01-3VINNOVASwedish Heart Lung Foundation, 20110589EU, FP7, Seventh Framework ProgrammeWenner-Gren FoundationsSwedish Society for Medical Research (SSMF)
Available from: 2015-12-09 Created: 2015-12-09 Last updated: 2017-12-01Bibliographically approved

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Carlström, MattiasPersson, A. Erik G.

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